Degenerative Disc Disease (DDD) of the lumbar spine is accompanied with structural failure of the disc. Seventy-five percent (75%) of all adults will experience lower back pain (LBP) secondary to DDD in the lumbar spine at some point in their lifetime.1,2 Fusion of the involved motion segments is currently of the most common surgical treatment of severe DDD.3-5 However, radiographic follow-up studies (from as early as one year following surgery) have revealed that as many as 80% of patients may develop progressive degeneration in the adjacent vertebral segments regardless of the method of fusion.6-9 Altered vertebral kinematics and intra-disc pressure have been generally assumed to be important biomechanical factors leading to the degenerative development 10,11. Therefore, a quantitative knowledge of the in-vivo vertebral motion and disc deformation in normal human spines and in pathological spines before and after fusion surgery is instrumental to reveal the biomechanical factors accompanied with DDD development process. However, a literature review revealed that there is no data reported on the intervertebral disc deformation in living human subjects. Recently, we have developed a combined dual fluoroscopic image system (DFIS) and MRI based modeling technique to measure in-vivo human intervertebral disc deformation under weightbearing conditions. In this exploratory R21 proposal, the overall goal is to determine the vertebral motion and intervertebral disc deformation during dynamic human body activities using the combined DFIS and MRI technique. Firstly, we will compare intervertebral disc deformation (compressive and shear) of the lumbar spines (L1-2, L2-3, L3-4 and L4-5) of normal subjects and patients with severe DDD before fusion surgery during dynamic symmetric and asymmetric weight-lifting activities. Secondly, we will accurately quantify and compare the compressive and shear deformation of the lumbar intervertebral discs of the DDD patients after surgical fusion with those measured before surgery and those of normal subjects during the same activities. The proposed research will be the first attempt to quantitatively determine in-vivo vertebral motion and lumbar intervertebral disc deformation in normal subjects and patients with severe DDD under functional dynamic loading conditions. The data will quantify the effect of DDD and surgical fusion of the DDD segment on the vertebral motion and deformation of the intervertebral disc along the dynamic lumbar spine motion path. Therefore, this research will provide guidelines for the improvement of current surgical modalities for the treatment of DDD patients so that post-operative degeneration of adjacent segments can be prevented. The data can also be invaluable for establishing objective functions for designing future disc replacement implants, dynamic stabilization systems, spine biologics or tissue engineered products that can accommodate physiological intervertebral disc deformation. PUBLIC HEALTH RELEVANCE: This proposed project will investigate the compressive and shear deformation of human lumbar intervertebral discs during dynamic weight-lifting activities. It will also determine the effect of surgical fusion of diseased L5-S1 disc on lumbar disc deformation at the adjacent vertebral levels. The obtained knowledge will not only provide insight into the disease process but will also be useful for improvement of treatment strategies.